(S)-(−)-1-(4-fluoroisoquinolin-5-yl)sulfonyl-2-methyl-1,4-homopiperazine hydrochloride is a compound represented by formula (1):
(see Patent Document 1) and assumes the form of anhydrous crystals which are water-soluble. The compound (1) is known to be a useful drug for preventing and treating cerebrovascular disorders such as cerebral infarction, cerebral hemorrhage, subarachnoidal hemorrhage, and cerebral edema, particularly for suppressing cerebrovasospasm-related diseases such as cerebral stroke (see Patent Document 1).
Conventionally, only (S)-(−)-1-(4-fluoroisoquinolin-5-yl) sulfonyl-2-methyl-1,4-homopiperazine hydrochloride anhydrous crystals (hereinafter may be referred to simply as “anhydrous crystals”) are known to be the crystal form of compound (1) (see Patent Document 1) . The anhydrous crystals have a water content, as determined through Karl Fischer's method, of 1 wt. % (hereinafter referred to simply as “%”) or less.
However, water content of the anhydrous crystals increases with elapsed time at 25° C. and a relative humidity (RH) of 92%, and eventually reaches about 40% (FIG. 5). When the anhydrous crystals are stored under humid conditions (relative humidity higher than 50%), the anhydrous crystal structure thereof changes due to a hygroscopic phenomenon, concomitant with change in volume of the crystals. In other words, the anhydrous crystals undergo change in crystal structure via a hygroscopic phenomenon.
As has been generally known, when a main drug component or an excipient has problematic hygroscopicity or other problems, change in weight and in crystal form of the compound occurs, resulting in change in volume, possibly causing changes in hardness and cracks in tablets. Such a phenomenon is disadvantageous in the production of tablets. Thus, from the viewpoint of drug preparation and storage of drugs, compounds free from problems in hygroscopicity and other properties are used. In addition, change in crystal form caused by water absorption may impair stability and bioavailability of the compound. As a compound which is required to have very high purity to be suitably used as a base material for a medicine, the above problems need to be solved.
Since the anhydrous crystals of compound (1) have a drawback of problematic hygroscopicity, the anhydrate must be stored under rigorous moisture control. However, such rigorous control is difficult to carry out in an actual situation. Thus, there is a demand for a compound to be used as base material for a medicine as described above which has low hygroscopicity and high storage stability.
Patent Document 1: International Publication WO 99/20620 pamphlet